Chromosome basis of heredity

Mr. Imakando C. I.
BScED (UNZA), MSc Ecology (PSU – Thailand)
 Main concept – Genes are on chromosomes
• The chromosomal theory of inheritance is the idea that genes, the
units of heredity, are physical in nature and are found in the
chromosomes

• The theory arose at the turn of the twentieth century, and became
one of the cornerstones of the modern understanding of genetics

• Mendel’s “hereditary factors” were genes, though this wasn’t known

at the time

• Today it can be shown that genes are located on chromosomes.

• By tagging isolated chromosomes with a flourescent dye that

highlights the genes, particular genes can be seen.
Example
Concept 1: Mendelian inheritance has its physical
basis in the behavior of chromosomes
• Mitosis and meiosis were first described in the late 1800s

• The chromosome theory of inheritance states:

– Mendelian genes have specific loci (positions) on chromosomes

– Chromosomes undergo segregation and independent assortment

• The behavior of chromosomes during meiosis was said to account for

Mendel’s laws of segregation and independent assortment
 Morgan’s Experimental Evidence - Scientific Inquiry

• The first solid evidence associating a specific gene with a specific

chromosome came from

• Thomas Hunt Morgan, an embryologist

• Morgan’s experiments with fruit flies provided convincing evidence

that chromosomes are the location of Mendel’s heritable factors
Morgan’s Choice of Experimental Organism

• Several characteristics make fruit flies a convenient organism for

genetic studies:

– They breed at a high rate - Single mating will produce hundreds of

offspring

– A generation can be bred every two weeks

– They have only four pairs of chromosomes

• Morgan noted wild type, or normal, phenotypes that were common
in the fly populations

• Traits alternative to the wild type are called mutant phenotypes

 Linking Behavior of a Gene’s Alleles with Behavior of a
Chromosome Pair

• In one experiment, Morgan mated male flies with white eyes

(mutant) with female flies with red eyes (wild type)

– The F1 generation all had red eyes

– The F2 generation showed the 3:1 red:white eye ratio, but only males had
white eyes

• Morgan determined that the white-eyed mutant allele must be

located on the X chromosome

• Morgan’s finding supported the chromosome theory of inheritance

 Sex-linked genes exhibit unique patterns of
inheritance
• In humans and some other animals, there is a chromosomal basis of sex
determination

The Chromosomal Basis of Sex

• In humans and other mammals, there are two varieties of sex chromosomes: a
larger X chromosome and a smaller Y chromosome

• Only the ends of the Y chromosome have regions that are homologous with the X
chromosome

• The SRY gene on the Y chromosome codes for the development of testes
• Females are XX, and males are XY

• Each ovum contains an X chromosome, while a sperm may contain

either an X or a Y chromosome

• Other animals have different methods of sex determination

 Inheritance of Sex-Linked Genes
• The sex chromosomes have genes for many characters unrelated to
sex

• A gene located on either sex chromosome is called a sex-linked gene

• In humans, sex-linked usually refers to a gene on the larger X

chromosome
Inheritance of Sex-Linked Genes
 Inheritance of Sex-Linked Genes

• Sex-linked genes follow specific patterns of inheritance

• For a recessive sex-linked trait to be expressed

– A female needs two copies of the allele

– A male needs only one copy of the allele

• Sex-linked recessive disorders are much more common in males than

in females
Inheritance of Sex-Linked Genes
 Inheritance of Sex-Linked Genes
• Some disorders caused by recessive alleles on the X chromosome in
humans:

– Color blindness – A mild disorder almost always inherited as an X-linked allele

– Duchenne muscular dystrophy - A human genetic disease caused by a sex-

linked recessive allele; characterized by progressive weakening and a loss of
muscle tissue

– Hemophilia – A human genetic disease caused by a sex-linked recessive allele,

resulting in the absence of one or more blood-clotting proteins; characterized
by excessive bleeding following injury
 Review question
• Qtn: Color blindness is a recessive sex-linked disorder. A female who
carries an allele for color blindness, but who is not color-blind, mates
with a male who has normal color vision. What is the probability that
they will have a son who is color-blind?

• Ans: If a carrier mates with a male who has normal color vision,
there is a 50% chance that each daughter will be a carrier like her
mother and a 50% chance that each son will have the disorder.
BARR BODIES
What is a Barr body? Why do human females
show a Barr body in their cells?
• A Barr body is a dense object lying along the inside of the nuclear
envelope in cells of female mammals, representing a highly
condensed, inactivated X chromosome.

• Female mammals, including humans, inherit two X chromosomes—

twice the number inherited by males; females show a Barr body in
their cells so that the cells of females and males have the same
effective dose (one copy) of most X-linked genes.
 X inactivation maintains the proper gene dosage.
How is the X chromosome inactivated?

• The selection of which X chromosome will form the Barr body occurs
randomly and independently in each embryonic cell present at the
time of X inactivation.
• Why can you say that all calico cats are females?
• The tortoiseshell gene is on the X chromosome, and the tortoiseshell
phenotype requires the presence of two different alleles, one for
orange fur and one for black fur. Normally, only females can have
both alleles, because only they have two X chromosomes.

• Calico cats: An animal with a blotched coat, usually white with black
and reddish patches
Mosaicism in Cats

Sometimes refered to as
the tortoiseshell gene
 Why can you say that all mosaic cats are
females?
• The tortoiseshell gene is on the X chromosome, and the tortoiseshell
phenotype requires the presence of two different alleles, one for
orange fur and one for black fur. Normally, only females can have
both alleles, because only they have two X chromosomes.
 LINKED GENES
Concept: Linked genes tend to be inherited together
because they are located near each other on the
same chromosome
• Each chromosome has hundreds or thousands of genes
• Defn: Genes located on the same chromosome that tend to be inherited
together
• These genes do not sort independently, but rather are transmitted as a unit
• What is the definition of a sex-linked gene? A gene located on either sex chromosome
• What are linked genes? Do linked genes sort independently?
• Linked genes are genes located close enough together on a chromosome that they tend to be inherited together.
These genes do not sort independently, but rather are transmitted as a unit. It is important to note that as Morgan’s
experiments illustrated, some mechanism (later discovered to be “crossing over”) occasionally breaks the linkage
between specific alleles of genes on the same chromosome.
 How Linkage Affects Inheritance

• Morgan did other experiments with fruit flies to see how linkage
affects inheritance of two characters

• Morgan crossed flies that differed in traits of body color and wing
size
• Morgan found that body color and wing size are usually inherited
together in specific combinations (parental phenotypes)

• He noted that these genes do not assort independently, and

reasoned that they were on the same chromosome
• However, nonparental phenotypes were also produced

• Understanding this result involves exploring genetic recombination,

the production of offspring with combinations of traits differing from
either parent
 Genetic Recombination and Linkage
• The genetic findings of Mendel and Morgan relate to the
chromosomal basis of recombination
 Recombination of Unlinked Genes: Independent
Assortment of Chromosomes
• Mendel observed that combinations of traits in some offspring differ
from either parent

• Offspring with a phenotype matching one of the parental phenotypes

are called parental types

• offspring with nonparental phenotypes (new combinations of traits)

are called recombinant types, or recombinants

• A 50% frequency of recombination is observed for any two genes on

different chromosomes
Recombination of Linked Genes: Crossing Over
• Morgan discovered that genes can be linked, but the linkage was
incomplete, as evident from recombinant phenotypes

• Morgan proposed that some process must sometimes break the

physical connection between genes on the same chromosome

• That mechanism was the crossing over of homologous chromosomes

 Mapping the Distance Between Genes Using
Recombination Data
• Alfred Sturtevant, one of Morgan’s students, constructed a genetic
map, an ordered list of the genetic loci along a particular
chromosome

• Sturtevant predicted that the farther apart two genes are, the higher
the probability that a crossover will occur between them and
therefore the higher the recombination frequency
 Mapping the Distance Between Genes Using
Recombination Data
• A linkage map is a genetic map of a chromosome based on
recombination frequencies

• Distances between genes can be expressed as map units; one map

unit, or centimorgan, represents a 1% recombination frequency

• Map units indicate relative distance and order, not precise locations
of genes
Mapping the Distance Between Genes Using
Recombination Data
 Mapping the Distance Between Genes Using
Recombination Data
• Genes that are far apart on the same chromosome can have a
recombination frequency near 50%

• Such genes are physically linked, but genetically unlinked, and

behave as if found on different chromosomes
 Mapping the Distance Between Genes Using
Recombination Data
• Sturtevant used recombination frequencies to make linkage maps of
fruit fly genes

• Using methods like chromosomal banding, geneticists can develop

cytogenetic maps of chromosomes

• Cytogenetic maps indicate the positions of genes with respect to

chromosomal features
Mapping the Distance Between Genes Using
Recombination Data
 Concept: Alterations of chromosome number or structure
cause some genetic disorders

• Large-scale chromosomal alterations often lead to spontaneous

abortions (miscarriages) or cause a variety of developmental
disorders
 Abnormal Chromosome Number
• In nondisjunction, pairs of homologous chromosomes do not
separate normally during meiosis

• As a result, one gamete receives two of the same type of

chromosome, and another gamete receives no copy
Abnormal Chromosome Number
 Abnormal Chromosome Number

• Aneuploidy results from the fertilization of gametes in which

nondisjunction occurred

• Offspring with this condition have an abnormal number of a

particular chromosome
 Abnormal Chromosome Number
• A monosomic zygote has only one copy of a particular chromosome

• A trisomic zygote has three copies of a particular chromosome

 Abnormal Chromosome Number
• Polyploidy is a condition in which an organism has more than two
complete sets of chromosomes

– Triploidy (3n) is three sets of chromosomes

– Tetraploidy (4n) is four sets of chromosomes

• Polyploidy is common in plants, but not animals

• Polyploids are more normal in appearance than aneuploids

 Alterations of Chromosome Structure
• Alterations in chromosome structure can lead to four types of
changes in chromosome structure:

– Deletion removes a chromosomal segment

– Duplication repeats a segment

– Inversion reverses a segment within a chromosome

– Translocation moves a segment from one chromosome to another

Alterations of Chromosome Structure
 Human Disorders Due to Chromosomal Alterations

• Alterations of chromosome number and structure are associated

with some serious disorders

• Some types of aneuploidy appear to upset the genetic balance less

than others, resulting in individuals surviving to birth and beyond

• These surviving individuals have a set of symptoms, or syndrome,

characteristic of the type of aneuploidy
 Down Syndrome (Trisomy 21)
• Down syndrome is an aneuploid condition that results from three
copies of chromosome 21

• It affects about one out of every 700 children born in the United
States

• The frequency of Down syndrome increases with the age of the

mother, a correlation that has not been explained
Down Syndrome (Trisomy 21)
Trisomy 21 – Down’s Syndrome
-characteristic facial features
-correctable heart defects
-short in stature
-short neck
-flat nasal bridge
-low ears
-open mouth
-mental retardation
- Atherosclerosis (hardening of
the arteries
 Trisomy 21 – Down’s Syndrome
The single most common genetic cause of moderate mental retardation

Maternal Age Frequency

at birth
15-19
1/1250
20-24
1/1400
25-29
1/1100
30 1/900
31 1/900
31 1/750
32 1/625
33 1/500
34 1/386
35 1/300
36 1/225
37 1/175
38 1/140
39 1/100
40 1/80 90%: Meiotic nondisjunction during meiosis II of oogenesis
41 1/65
42 1/50 10%: Meiotic nondisjunction during meiosis I of spermatogenesis
Trisomy 18 -  Edwards syndrome

-1:10,000 live births

-failure to thrive
-severe heart malformations
-hypotonia
-clenched fists
-rocker bottom feet
-survival beyond a
few months is rare
 Trisomy 13 – Patau syndrome
• Having extra genetic material from
chromosome 13

• 1:5,000 live births

• growth retardation

• severe CNS

• malformations

• cleft lip/palate

• congenetial heart defects

• not compatible with survival

 Aneuploidy of Sex Chromosomes
• Nondisjunction of sex chromosomes produces a variety of aneuploid
conditions

• Klinefelter syndrome is the result of an extra chromosome in a male,

producing XXY individuals

• Monosomy X, called Turner syndrome, produces X0 females, who

are sterile; it is the only known viable monosomy in humans
 Klinefelter’s Syndrome

XXY – Phenotypically
male with an extra X
chromosome
1-in-500 to 1-in-1000 male births
 Trisomy X (XXX Syndrome)
• May be taller than average, this chromosomal change typically causes
no unusual physical features

• Normal sexual development and are able to conceive children

• associated with an increased risk of learning disabilities and delayed

development of speech and language skills

• Delayed development of motor skills (such as sitting and walking), weak

muscle tone (hypotonia), and behavioral and emotional difficulties are
also possible

• Seizures or kidney abnormalities occur in about 10 percent of affected

females.
 Turner’s Syndrome (Monosomy X)
• XO – Phenotypically
female missing an X
chromosome
• 1 in 5,000 phenotypic
female
• It’s the only known
viable monosomy in
humans
• Sterile – sex organs do
not mature
• Most have normal
intelligence
 Disorders Caused by Structurally Altered
Chromosomes
• Many deletions in human chromosomes, even in a heterozygous
state cause severe problems.

• The syndrome cri du chat (“cry of the cat”), results from a specific
deletion in chromosome 5

• A child born with this syndrome is mentally retarded and has a

catlike cry; individuals usually die in infancy or early childhood
 Disorders Caused by Structurally Altered
Chromosomes

• Certain cancers, including chronic myelogenous leukemia (CML), are

caused by translocations of chromosomes
Figure 8.20A_s1
MEIOSIS I

Nondisjunction
Figure 8.20A_s2
MEIOSIS I

Nondisjunction

MEIOSIS II

Normal
meiosis II
Figure 8.20A_s3
MEIOSIS I

Nondisjunction

MEIOSIS II

Normal
meiosis II

Gametes

Number of n1 n1 n1 n1

chromosomes
Abnormal gametes
Figure 8.20B_s1
MEIOSIS I

Normal
meiosis I
Figure 8.20B_s2
MEIOSIS I

Normal
meiosis I

MEIOSIS II

Nondisjunction
Figure 8.20B_s3
MEIOSIS I

Normal
meiosis I

MEIOSIS II

Nondisjunction

n1 n1 n n

Abnormal gametes Normal gametes

Abnormal Chromosome Number
 Some inheritance patterns are
exceptions to the standard chromosome
theory
 Some inheritance patterns are exceptions to the
standard chromosome theory
• There are two normal exceptions to Mendelian genetics

• One exception involves genes located in the nucleus, and

• The other exception involves genes located outside the nucleus

• The sex of the parent contributing an allele is a factor in the pattern of

inheritance.

1. Genomic imprinting

2. Inheritance of organelle genes

 Genomic Imprinting
• According to Mendelian genetics a given allele will have the same
effect whether it was inherited from the mother or the father

• e.g. RR x rr

• For a few mammalian traits, the phenotype depends on which parent

passed along the alleles for those traits

• Genomic imprinting – the variation in phenotype depending on

whether an allele is inherited from the male or female parent.
 Genomic Imprinting
• Unlike sex-linked genes, most imprinted genes are on autosomal
chromosomes
 Genomic Imprinting
• Occurs during oogenesis or spermatogenesis and results in the
silencing of a particular allele of a certain gene

• In a zygote only one allele (either from male or female parent) of the
imprinted gene is expressed, the other is silenced.

• This is because these imprinted genes are imprinted differently in

sperms and eggs.

• Imprinted genes are heritable and they tend to show a specific

pattern for a given species
 Genomic imprinting
• Genomic imprinting is thought to affect only a small fraction of
mammalian genes

• Most imprinted genes are critical for embryonic development

 Genomic Imprinting in Mice –
Insulin-like growth factor 2 (Igf2)

• A mouse homozygous for the wild-type Igf2 allele is normal sized.

• In this case only the paternal allele of this gene is expressed

 Genomic Imprinting in Mice
• Lets assume that we crossed two homozygotes (a wild type and a
recessive mutant.

• The mutant (dwarf) phenotype is seen only when the father

contributed the mutant allele because the maternal allele is not
expressed
 Genomic Imprinting in Mice
• Lets assume that we crossed two heterozygotes (a wild type and a recessive mutant.

• The mutant (dwarf) phenotype is seen only when the father contributed the mutant allele
because the maternal allele is not expressed

Note: normal development of an organisms inheriting an imprinted

gene seems to require that embryonic cells have exactly one active
copy – not zero, note two
 What causes genomic imprinting
• It appears that imprinting is the result of the methylation (addition of
–CH3) of DNA

• Specifically methyl groups are added to cytosine nucleotides of one

of the alleles (actually heavily genes are usually inactive)
 Inheritance of Organelle Genes
• Extranuclear genes (or cytoplasmic genes) are genes found in organelles in
the cytoplasm

• Mitochondria, chloroplasts, and other plant plastids (in plants) carry small
circular DNA molecules

• Extranuclear genes are inherited maternally because the zygote’s cytoplasm

comes from the egg

• The first evidence of extranuclear genes came from studies on the

inheritance of yellow or white patches on leaves of an otherwise green plant
• Variegated (striped or spotted) leaves result from mutations in
pigment genes located in plastids, which generally are inherited from
the maternal parent.
 You should now be able to:
1. Explain the chromosomal theory of inheritance and its discovery

2. Explain why sex-linked diseases are more common in human males

than females

3. Distinguish between sex-linked genes and linked genes

4. Explain how meiosis accounts for recombinant phenotypes

5. Explain how linkage maps are constructed

 You should now be able to:
6. Explain how nondisjunction can lead to aneuploidy

7. Define trisomy, triploidy, and polyploidy

8. Distinguish among deletions, duplications, inversions, and

translocations

9. Explain genomic imprinting

10. Explain why extranuclear genes are not inherited in a Mendelian

fashion